The development of immunocompetent lymphocytes and their differentiation into activated effector cells upon contact with foreign molecular structures provides a complex but accessible model of differentiation. Interest in this model is more than academic, for within it lies the key to regulation of allograft and tumor immunity. The broad objective of the proposed research is to examine the mechanics and pathways of T-cell differentiation from the earliest phase thus far established (pro-thymocyte) to the effector stage. The study will elucidate the several stages of T cell differentiation (e.g., construct a "differentiative tree" for thymus-derived lymphocytes) in terms of surface membrane markers expressed and commitment to specialized function. The approach will involve utilization of several membrane probes - including Fc receptors, Ly, Ia and ThB determiniants - to identify the T cell subsets and a fluorescence Activated Cell Sorter (FACS) to isolate these subsets. The study will examine mechanisms by which each phase of differentiation is regulated in terms of a) the molecular and/or cellular components of the regulatory system; b) the specificity of the regulatory events with respect to the phase of differentiation affected by the regulatory event, the factors which are conducive to or instigate the regulatory event; c) the genetic basis for regulation; and d) the involvement (or identity?) of these regulatory mechanisms in the phenomenon of immunological surveillance.